Epidemiological studies have suggested that exposure to drugs such as nicotine and marijuana during adolescence is correlated with a significantly higher incidence of subsequent use of other drugs such as cocaine. In addition, there are different responses between female and male adolescents in response to drug use.Animal laboratory studies have shown that female and male rats respond differently to drugs and that the neurochemical adaptations that occur also differ. Studies have shown that drug administration during adolescence leads to differential neurochemical and behavioral effects than drug administration during adulthood. In addition, many of the effects of drugs during this critical developmental period have long- lasting effects that persist into adulthood. In general, the studies suggest that there may be an increased vulnerability to the effects of drugs during adolescence and that the effects differ across both sex andage. The main hypothesis of this proposal is that females and males will respond differently to drugs during different stages of development and that it may therefore be necessary to develop sex-and age-specific treatments for drug addiction. The focus of this proposal is to study the effects of nicotine, marijuana(A9- THC) and cocaine in female and male adolescent and adult rats on behavior and neurochemistry during adolescence and later during adulthood. In addition, the effects of environment on the changes produced by these drugs will be examined. An understanding of the differential effects of drugs in females and males during adolescence, and of how these changes use impact drug effects in adults may lead to sex-andage- specific treatments for drug addiction.